Ferrets are susceptible to infection with human influenza virus and show symptoms that mimic those seen in humans making them a useful laboratory model (Maher J. Lab Animal 2004; 33(9): 50-53; Van der Laan J, Herberts R, Lanbkin-Williams R, Boyers A, Mann A, Oxford J. Expert Rev Vaccines 2008; 7(6): 783-793). For this reason, ferrets have routinely been used to study the effects of influenza vaccines. A more recent application has been the study of human monoclonal antibodies directed against influenza viruses in ferrets (Friesen R, Koudstaal W, Koldijk M, et al PLOS One 2010; 5(2): e9106). However, this and another study involving ferrets exposed to the Nipah virus (Bossart K, Zhu Z, Middleton D, et al. PLOS Pathog 2009; 5(10): e1000642) suggested that ferrets have an antibody clearance rate much faster than other commonly-used model species such as mice, rats and cynomolgus monkeys (Petkova S, Akilesh S, Sproule T J, et al. Int. Immunol. 2006; 18 (12): 1759-1769; Lin S Y, Cindy Nguyen C, Mendoza J L, et al. JPET 1999; 288 (1): 371-378).
This illustrates the critical limitations of the ferret model for use in the testing of monoclonal antibody therapeutics. The short half-life of human antibody therapeutics in the ferret necessitates high dosing frequency, increasing material requirements, thereby demanding greater resources. Moreover, a misunderstanding of the PK-PD relationship for fast-clearing antibodies may lead to misinterpretation of efficacy results. Thus, there is a need in the art to develop novel IgG variants with reduced immunogenicity and longer circulating half-life in ferrets. The present application meets these and other needs.